(Left – right) Dr Gary Wong, Dr Hong-lok Lung, Miss Lijun Jiang and Professor Nai-ki Mak and their collaborators are the first in the world to develop a compound to enhance the detection of tumour cells and inhibit their growth in mice – providing insights into the development of therapeutics for use against EBV-associated diseases. Photo credit: HKBU

Scholars at Hong Kong Baptist University (HKBU) along with their collaborators recently announced the world’s first chemical compound (probe) that can simultaneously detect and inhibit Epstein-Barr virus (EBV)-infected tumour cells in mice, with an efficacy rate of above 90%.

The groundbreaking discovery is expected to lay a foundation for the development of therapeutics for use against diseases associated with EBV, including nasopharyngeal carcinoma, which is prevalent in Southern China. The study was published in the international journal Nature Biomedical Engineering.

Enhancing efficacy of targeted therapeutics

The study showed that the probe containing the inhibitor luminesces when bound to the EBV encoded viral protein EBNA1 of EBV-infected cells in mice. Hence, it could be applied as an agent to detect the presence of tumours.

In addition, the probe can prevent the formation of EBNA1 homodimer, as the study showed that the probe results in a 93% reduction in size of EBV-positive tumours in mice.

Diagram showing the use of the designed probe for imaging and inhibition of EBV-infected tumours. Photo credit: HKBU

“The establishment of EBV latency is closely associated with the oncogenic development of several human malignancies, including nasopharyngeal carcinoma. In the past few decades, EBNA1 has been considered an attractive target for anti-viral therapy, attracting a great deal of attention from researchers working in this community. Several studies on the inhibition of EBNA1, a dual-probe to track the EBNA1 at the nucleus level, were published but an agent with dual functions is still not yet available. Our team has developed the world’s first dual agent that can simultaneously perform imaging and suppress EBV-associated tumours,” says Dr Gary Wong, Associate Professor of HKBU Department of Chemistry, and one of the leaders of the research team.

The research team was also led by Professor Nai-ki Mak, Professor of HKBU Department of Biology, and collaborators from other departments at HKBU, The Hong Kong Polytechnic University, The University of Hong Kong, and Durham University and University of Birmingham in the United Kingdom.

With further development, Wong believes this probe could potentially be applied to the imaging of tumour cells in the human body and lead to the development of therapeutics. Ultimately, this enhances the overall efficacy of targeted therapeutics.

The study shows that the probe can lead to 93% growth inhibition of EBV-positive tumours in mice: (above) control tumour; (below) tumour showing a 93% reduction in size. Photo credit: HKBU

Wong envisaged that scientists could make further developments on such probes since the zinc finger structure in EBNA1 homodimer is thought to contribute to the formation of EBNA1 homodimer. MIMS